Is Mitochondiral STAT3 Necessary For K-Ras Induced Myeloid Leukaemias?
Funder
National Health and Medical Research Council
Funding Amount
$425,326.00
Summary
Myeloid leukaemia (ML) is a family of diseases characterized by the expansion of white blood cells, leading to death from haematopoietic complications. One common mutation that gives a proliferative advantage in ML is in the Ras oncogenes. We recently showed that signal transducer and activator of transcription 3 (STAT3) is necessary for the transforming potential of Ras due to its ability to support the metabolic changes necessary for tumour growth. This research will characterize the STAT3-dep ....Myeloid leukaemia (ML) is a family of diseases characterized by the expansion of white blood cells, leading to death from haematopoietic complications. One common mutation that gives a proliferative advantage in ML is in the Ras oncogenes. We recently showed that signal transducer and activator of transcription 3 (STAT3) is necessary for the transforming potential of Ras due to its ability to support the metabolic changes necessary for tumour growth. This research will characterize the STAT3-dependent metabolic changes in ML.Read moreRead less
Wbp2, A New Regulator Of The Hippo Tumor Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which a newly-identified Hippo pathway protein, Wbp2, functions to control growth. These studies will be performed in flies and confirmed in mammalian cells. Ultimately, our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Achieving More Effective Weight Loss With Intermittent Energy Restriction
Funder
National Health and Medical Research Council
Funding Amount
$1,373,874.00
Summary
Part of the difficulty in achieving lasting weight loss is that the body responds to dieting with compensatory changes in appetite, metabolic rate & blood hormone levels. We have shown in men that alternating phases of energy restriction with periods of greater food intake markedly improves weight loss by overcoming this “famine reaction”. This study will examine if the intermittent diet also produces more effective weight loss in women, and whether it is applicable to the wider community.
Identification Of Novel Tumour Suppressors In Ras-mediated Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$580,504.00
Summary
Cancer is a cooperative process, involving mutations in several genes. Activation of the signaling protein, Ras, contributes to ~30% of human cancers, but alone is not sufficient for tumour formation. The identification of cooperating Tumour Suppressors (TSs), and their analysis in the vinegar fly, Drosophila, mammalian cells and mouse models is key to understanding cancer progression and for the development of therapeutic regimes
Age- And Energy-status Dependent-plasticity Of Glucose Sensing, Orexigenic NPY Neurons: The Glucose-ghrelin Balance
Funder
National Health and Medical Research Council
Funding Amount
$578,641.00
Summary
Our research aims to identify how specific brain cells detect changes in glucose levels and how ageing and diet affect their function. We identified a subset of nerve cells that detect changes in glucose and the “hunger” hormone ghrelin, their ability to do so adapting with age and nutritional status. This project will investigate the potential of these nerve cells as targets for therapeutic and diet- intervention strategies to target obesity, diabetes and promote healthy ageing
Brain Glucose-sensing: Age- And Energy-status-dependent Plasticity Of Function-specific Pro-opiomelanocortin (POMC) Glucose-sensing Neurons In The Arcuate Nucleus Of The Hypothalamus
Funder
National Health and Medical Research Council
Funding Amount
$495,071.00
Summary
Obesity and ageing predispose individuals to diabetes, the health and socio-economic implications of which posing significant challenges for Australia in the foreseeable future. Research outlined here aims to identify novel mechanisms enabling brain cells to detect changes in glucose and how ageing and diet affect the function of these nerves. We believe this research could provide novel therapeutic and early diet-based intervention strategies for diabetes and obesity.
Targeting Of The Myb-p300 Interaction In Myeloid Leukaemogenesis
Funder
National Health and Medical Research Council
Funding Amount
$625,980.00
Summary
MYB is a “cancer gene” which turns other genes on or off. MYB is needed by leukaemia cells but also for normal blood cell formation. This project aims to show that blocking interaction between the MYB protein and another protein called p300 is a promising strategy for leukaemia treatment, as leukaemia cells are more dependent on this interaction than normal cells. New molecules to block the MYB-p300 interaction will also be designed and tested; these may form a basis for new leukaemia drugs.
NPY Coordination Of Energy Balance And Physical Activity
Funder
National Health and Medical Research Council
Funding Amount
$844,596.00
Summary
Anorexia nervosa (AN) is an eating disorder characterized by behavioral alterations, restrictive eating leading to extremely low body weight. AN is also associated with a paradoxical hyperactivity representing a failure of the brain to adjust activity to energy status. Here we aim to investigate the role of the Neuropeptide Y (NPY), a known regulator of homeostatic control and activity in the development of hyperactivity in AN, thus help to identify NPY-targeted therapeutics for AN treatment.
Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.
Genetic Fate Mapping Of Mesenchymal Stem Cell Origins And Investigating Their Contribution To Developmental Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$611,525.00
Summary
Mesenchymal stem cells are a population of cells that reside in various organs in the body and are thought to contribute to tissue repair. However little is known about the developmental origins and identity of these cells. I will investigate where these cells originate from, their molecular identity and how they relate to blood development. These findings will help in developing protocols to manipulate these cells to repair damaged organs. This study will also inform current attempts to generat ....Mesenchymal stem cells are a population of cells that reside in various organs in the body and are thought to contribute to tissue repair. However little is known about the developmental origins and identity of these cells. I will investigate where these cells originate from, their molecular identity and how they relate to blood development. These findings will help in developing protocols to manipulate these cells to repair damaged organs. This study will also inform current attempts to generate blood stem cells.Read moreRead less